WO2008109156A3 - Process for the preparation of quaternary n-alkyl morphinan alkaloid salts - Google Patents

Process for the preparation of quaternary n-alkyl morphinan alkaloid salts Download PDF

Info

Publication number
WO2008109156A3
WO2008109156A3 PCT/US2008/003070 US2008003070W WO2008109156A3 WO 2008109156 A3 WO2008109156 A3 WO 2008109156A3 US 2008003070 W US2008003070 W US 2008003070W WO 2008109156 A3 WO2008109156 A3 WO 2008109156A3
Authority
WO
WIPO (PCT)
Prior art keywords
quaternary
preparation
morphinan alkaloid
alkaloid salts
alkyl morphinan
Prior art date
Application number
PCT/US2008/003070
Other languages
French (fr)
Other versions
WO2008109156A2 (en
Inventor
Peter X Wang
Robert E Halvachs
Kevin R Roesch
Henry J Buehler
Joseph P Haar
Original Assignee
Mallinckrodt Inc
Cantrell Gary L
Peter X Wang
Robert E Halvachs
Kevin R Roesch
Henry J Buehler
Joseph P Haar
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to EP20080726581 priority Critical patent/EP2137189B1/en
Application filed by Mallinckrodt Inc, Cantrell Gary L, Peter X Wang, Robert E Halvachs, Kevin R Roesch, Henry J Buehler, Joseph P Haar filed Critical Mallinckrodt Inc
Priority to NZ579469A priority patent/NZ579469A/en
Priority to AU2008223328A priority patent/AU2008223328B2/en
Priority to US12/529,723 priority patent/US8669366B2/en
Priority to JP2009552750A priority patent/JP5875748B2/en
Priority to ES08726581.5T priority patent/ES2540534T3/en
Priority to CA2680205A priority patent/CA2680205C/en
Priority to PL08726581T priority patent/PL2137189T3/en
Publication of WO2008109156A2 publication Critical patent/WO2008109156A2/en
Publication of WO2008109156A3 publication Critical patent/WO2008109156A3/en
Priority to US12/553,144 priority patent/US9040726B2/en
Priority to AU2009227892A priority patent/AU2009227892B2/en
Priority to US14/569,309 priority patent/US9415044B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
    • C07D489/08—Oxygen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
    • C07D489/04—Salts; Organic complexes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Abstract

An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.
PCT/US2008/003070 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts WO2008109156A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
ES08726581.5T ES2540534T3 (en) 2007-03-06 2008-03-06 Procedure for the preparation of quaternary salts of N-alkyl morphinan alkaloids
NZ579469A NZ579469A (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
AU2008223328A AU2008223328B2 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
US12/529,723 US8669366B2 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
JP2009552750A JP5875748B2 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
EP20080726581 EP2137189B1 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
CA2680205A CA2680205C (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
PL08726581T PL2137189T3 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
US12/553,144 US9040726B2 (en) 2007-03-06 2009-09-03 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
AU2009227892A AU2009227892B2 (en) 2007-03-06 2009-10-21 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
US14/569,309 US9415044B2 (en) 2007-03-06 2014-12-12 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US89316307P 2007-03-06 2007-03-06
US60/893,163 2007-03-06
US95324807P 2007-08-01 2007-08-01
US60/953,248 2007-08-01

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/553,144 Continuation US9040726B2 (en) 2007-03-06 2009-09-03 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts

Publications (2)

Publication Number Publication Date
WO2008109156A2 WO2008109156A2 (en) 2008-09-12
WO2008109156A3 true WO2008109156A3 (en) 2008-11-20

Family

ID=39720102

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/003070 WO2008109156A2 (en) 2007-03-06 2008-03-06 Process for the preparation of quaternary n-alkyl morphinan alkaloid salts

Country Status (10)

Country Link
US (1) US8669366B2 (en)
EP (2) EP2137189B1 (en)
JP (5) JP5875748B2 (en)
CN (1) CN101781303A (en)
AU (2) AU2008223328B2 (en)
CA (2) CA2707757C (en)
ES (2) ES2598140T3 (en)
NZ (2) NZ579469A (en)
PL (2) PL2137189T3 (en)
WO (1) WO2008109156A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102558188B (en) * 2010-12-17 2014-07-23 北大方正集团有限公司 Preparation method of methyhaaltrexone bromide
US9518062B2 (en) 2009-07-16 2016-12-13 Mallinckrodt Llc Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2008223328B2 (en) * 2007-03-06 2012-10-11 SpecGx LLC Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
MX351611B (en) 2007-03-29 2017-10-20 Wyeth Llc Crystal forms of (r) -n-methylnaltrexone bromide and uses thereof.
WO2009009292A2 (en) * 2007-07-11 2009-01-15 Mallinckrodt Inc. Crystalline forms of naltrexone methobromide
CN101959892B (en) * 2008-02-06 2014-01-08 普罗热尼奇制药公司 Preparation and use of (R),(R)-2,2'-bis-methylnaltrexone
UA102128C2 (en) * 2008-12-05 2013-06-10 Х. Луннбек А/С Nalmefene hydrochloride dihydrate
TWI541246B (en) 2008-12-08 2016-07-11 歐陸斯迪公司 Dihydroetorphine
JP5784507B2 (en) * 2009-02-23 2015-09-24 マリンクロッド エルエルシー (+)-Morphinanium quaternary salt and method for producing the same
NZ595591A (en) 2009-04-24 2013-11-29 Univ Brock Processes for the preparation of morphinane and morphinone compounds
CN101845047B (en) * 2009-12-31 2011-12-07 南京臣功制药有限公司 Method for preparing methylnaltrexone bromide
AU2011263416B2 (en) 2010-06-11 2014-04-10 Rhodes Technologies Process for N-dealkylation of tertiary amines
TWI478928B (en) 2010-06-11 2015-04-01 Rhodes Technologies Transition metal-catalyzed processes for the preparation of n-allyl compounds and use thereof
GB201309654D0 (en) 2013-05-30 2013-07-17 Euro Celtique Sa Method
ES2784690T3 (en) 2013-12-05 2020-09-29 Univ Bath New opioid compounds and their uses
CN103626782B (en) * 2013-12-13 2016-07-13 山东新华制药股份有限公司 The preparation method of methylnaltrexone bromide
TWI546074B (en) * 2014-01-15 2016-08-21 羅德科技公司 Process for improved oxycodone synthesis
CN105753874A (en) * 2014-12-15 2016-07-13 北大方正集团有限公司 Delta-7 methylnaltrexone formate and preparation method thereof
CN105753875A (en) * 2014-12-15 2016-07-13 北大方正集团有限公司 Acetylated Delta-7 methylnaltrexone formate and preparation method thereof
CN105777766B (en) * 2014-12-15 2017-11-24 北大方正集团有限公司 The preparation method of the methylnaltrexone bromides of Delta 7
CN106317064B (en) * 2015-06-30 2018-06-19 北大方正集团有限公司 The preparation method of methylnaltrexone bromide
CN110272398B (en) 2018-03-16 2022-11-29 江苏瑞科医药科技有限公司 Process for producing hexahydrofurofuranol derivative, intermediate therefor, and process for producing the intermediate

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4176186A (en) * 1978-07-28 1979-11-27 Boehringer Ingelheim Gmbh Quaternary derivatives of noroxymorphone which relieve intestinal immobility
ES2121554A1 (en) * 1996-12-23 1998-11-16 Univ Santiago Compostela Process for obtaining 14-hydroxymorphines by the photo- oxidation of morphine alkaloids with an alkoxydiene system in the C ring
EP0897726A1 (en) * 1996-11-25 1999-02-24 Toray Industries, Inc. Antipruritic agent
WO2004029059A1 (en) * 2002-09-25 2004-04-08 Euro-Celtique S.A. N-substituted hydromorphones and the use thereof
WO2004043964A2 (en) * 2002-11-08 2004-05-27 Mallinckrodt Inc. Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
WO2006127899A2 (en) * 2005-05-25 2006-11-30 Progenics Pharmaceuticals, Inc. (r)-n-methylnaltrexone, processes for its synthesis and its pharmaceutical use
WO2006127898A2 (en) * 2005-05-25 2006-11-30 Progenics Pharmaceuticals, Inc. (s)-n-methylnaltrexone, process for its synthesis and its pharmaceutical use

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3101339A (en) * 1958-10-30 1963-08-20 Boehringer Sohn Ingelheim Quaternary salts of normorphine and its acylated derivatives
US4141897A (en) * 1976-12-20 1979-02-27 Research Corporation N-dealkylation of N-alkyl-14-hydroxymorphinans and derivatives thereof
FR2469413B1 (en) 1979-11-13 1986-04-25 Urpha 6H-DIBENZO (A, G) 5,8,13,13A-TETRAHYDROQUINOLIZINE DERIVATIVES, PROCESS FOR OBTAINING AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US4322426A (en) * 1980-04-28 1982-03-30 E. I. Du Pont De Nemours And Company 17-Substituted-6-desoxy-7,8-dihydro-6α-methylnoroxymorphone narcotic antagonists
US4410700A (en) * 1980-07-03 1983-10-18 The United States Of America As Represented By The Department Of Health And Human Services Preparation of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines by optical resolution
US4727146A (en) * 1980-07-03 1988-02-23 The United States Of America As Represented By The Department Of Health And Human Services Synthesis of chiral 1-benzyl-1,2,3,4-tetra-hydroisoquinolines by asymmetric reduction
US4556712A (en) * 1981-05-20 1985-12-03 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Preparation and racemization of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines
US4368326A (en) * 1980-07-03 1983-01-11 Rice Kenner C Short total synthesis of dihydrothebainone, dihydrocodeinone, and nordihydroccodeinone
US4521601A (en) * 1981-05-20 1985-06-04 The United States Of America As Represented By The Department Of Health & Human Services Practical total synthesis unnatural enantiomers of opium-derived morphinans
US4535157A (en) * 1983-11-01 1985-08-13 Key Pharmaceuticals, Inc. Process for making 6-desoxy-6-methylenenaloxone and 6-desoxy-6-methylenenaltrexone
JPS60132983A (en) * 1983-12-21 1985-07-16 Tanabe Seiyaku Co Ltd Thiazoleacetic acid derivative and its production
US4613668A (en) * 1983-12-22 1986-09-23 The United States Of America As Represented By The Department Of Health And Human Services Short total synthesis or morphinan compounds which uses cyclization of a cycloalkylcarbonyl compound selected from cyclopropylcarbonyl and cyclobutylcarbonyl
US5112975A (en) * 1984-03-27 1992-05-12 Mallinckrodt Specialty Chemicals Company Preparation of noroxymorphone from morphine
US5668285A (en) * 1986-10-31 1997-09-16 The United States Of America As Represented By The Department Of Health And Human Services Total synthesis of northebaine, normophine, noroxymorphone enantiomers and derivatives via N-Nor intermediates
US5352780A (en) * 1989-07-20 1994-10-04 Ecosorb International, Inc. Absorbent material and litter from ground cellulose
DE4132159A1 (en) * 1991-09-27 1993-04-01 Boehringer Ingelheim Kg 14-HYDROXY-N- (2-METHOXYETHYL) -7,8-DIHYDROMORPHINE AND -NORISOMORPHINE, PROCESS FOR THEIR PREPARATION AND THEIR USE AS DRUG
US5574159A (en) 1992-02-03 1996-11-12 Delta Pharmaceuticals, Inc. Opioid compounds and methods for making therefor
US5352680A (en) 1992-07-15 1994-10-04 Regents Of The University Of Minnesota Delta opioid receptor antagonists to block opioid agonist tolerance and dependence
AU5171293A (en) * 1992-10-14 1994-05-09 Regents Of The University Of Colorado, The Ion-pairing of drugs for improved efficacy and delivery
DE4333892A1 (en) * 1993-10-05 1995-04-06 Brose Fahrzeugteile Manually actuable mechanical memory device
SE9401728D0 (en) * 1994-05-18 1994-05-18 Astra Ab New compounds II
US5869669A (en) * 1996-07-26 1999-02-09 Penick Corporation Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates
US5756851A (en) * 1996-10-21 1998-05-26 Albemarle Corporation Production of nabumetone or precursors thereof
GB9713703D0 (en) * 1997-06-30 1997-09-03 Johnson Matthey Plc Preparation of opiates
ES2172376B1 (en) 2000-01-28 2003-11-16 Servier Lab NEW DERIVATIVES OF ISOQUINOLEINS, ITS PREPARATION PROCEDURE AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
DE10229842A1 (en) * 2002-07-03 2004-02-05 Helmut Prof. Dr. Schmidhammer Morphinane derivatives and their quaternary ammonium salts substituted in position 14, production process and use
SI1864987T1 (en) * 2004-02-06 2010-04-30 Euro Celtique Sa Methods for making 3-O protected morphinones and 3-O-protected morphinone dienol carboxylates
WO2006084389A1 (en) * 2005-02-11 2006-08-17 Cilag Ltd. Method for purifying noroxymorphone compounds
JP2008546688A (en) * 2005-06-16 2008-12-25 マリンクロッド・インコーポレイテッド Synthetic route to 14-hydroxyl opiates via 1-halo-thebaine or analogs
EP2101773A2 (en) * 2006-11-22 2009-09-23 Progenics Pharmaceuticals, Inc. (r)-n-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs
AU2008223328B2 (en) * 2007-03-06 2012-10-11 SpecGx LLC Process for the preparation of quaternary N-alkyl morphinan alkaloid salts

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4176186A (en) * 1978-07-28 1979-11-27 Boehringer Ingelheim Gmbh Quaternary derivatives of noroxymorphone which relieve intestinal immobility
EP0897726A1 (en) * 1996-11-25 1999-02-24 Toray Industries, Inc. Antipruritic agent
ES2121554A1 (en) * 1996-12-23 1998-11-16 Univ Santiago Compostela Process for obtaining 14-hydroxymorphines by the photo- oxidation of morphine alkaloids with an alkoxydiene system in the C ring
WO2004029059A1 (en) * 2002-09-25 2004-04-08 Euro-Celtique S.A. N-substituted hydromorphones and the use thereof
WO2004043964A2 (en) * 2002-11-08 2004-05-27 Mallinckrodt Inc. Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
WO2006127899A2 (en) * 2005-05-25 2006-11-30 Progenics Pharmaceuticals, Inc. (r)-n-methylnaltrexone, processes for its synthesis and its pharmaceutical use
WO2006127898A2 (en) * 2005-05-25 2006-11-30 Progenics Pharmaceuticals, Inc. (s)-n-methylnaltrexone, process for its synthesis and its pharmaceutical use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CROOKS ET AL: "Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 16, no. 16, 15 August 2006 (2006-08-15), pages 4291 - 4295, XP005544067, ISSN: 0960-894X *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9518062B2 (en) 2009-07-16 2016-12-13 Mallinckrodt Llc Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers
CN102558188B (en) * 2010-12-17 2014-07-23 北大方正集团有限公司 Preparation method of methyhaaltrexone bromide

Also Published As

Publication number Publication date
PL2137189T3 (en) 2015-12-31
AU2009227892A1 (en) 2009-11-12
JP2010520288A (en) 2010-06-10
EP2147920A2 (en) 2010-01-27
CA2707757A1 (en) 2008-09-12
EP2147920A3 (en) 2010-03-24
EP2147920B1 (en) 2016-08-31
CA2680205A1 (en) 2008-09-12
PL2147920T3 (en) 2017-02-28
AU2008223328B2 (en) 2012-10-11
JP2015052019A (en) 2015-03-19
JP5957180B2 (en) 2016-07-27
EP2137189A2 (en) 2009-12-30
ES2598140T3 (en) 2017-01-25
CA2680205C (en) 2015-06-30
US8669366B2 (en) 2014-03-11
CN101781303A (en) 2010-07-21
US20110082297A1 (en) 2011-04-07
NZ580536A (en) 2010-11-26
CA2707757C (en) 2017-01-03
WO2008109156A2 (en) 2008-09-12
JP2016210815A (en) 2016-12-15
AU2009227892B2 (en) 2012-09-27
JP5875748B2 (en) 2016-03-02
AU2008223328A1 (en) 2008-09-12
JP2013216687A (en) 2013-10-24
EP2137189B1 (en) 2015-05-06
ES2540534T3 (en) 2015-07-10
JP2011098988A (en) 2011-05-19
NZ579469A (en) 2011-02-25

Similar Documents

Publication Publication Date Title
WO2008109156A3 (en) Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
ZA201103480B (en) Methods of preparing quinoline derivatives
HK1196615A1 (en) Process for preparing heterocyclic compounds including trans-7-oxo-6- (sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof -7--6-()-16-[321]-2-
HK1158628A1 (en) Process for preparing dihydropteridinone derivatives
EP2169075A4 (en) Method for production of alkaloid
EP2358691B8 (en) Process for the preparation of piperazine compounds and hydrochloride salts thereof
IL214426A0 (en) [1,2,4] triazollo [1,5-a] pyridines as kinase inhibitors
WO2010001257A3 (en) Novel solid state forms of laquinimod and its sodium salt
WO2009151899A3 (en) Preparation of imatinib mesylate
EP2639234A4 (en) Crystalline 6,7-unsaturated-7-carbamoyl morphinane derivative, and method for producing same
IL210074A (en) Process for the preparation of derivatives of pyrido[2,3-d]pyrimidine-7-yl-phenyl
PL2213654T3 (en) Process for preparing 2-amino-5-bromobenzamide derivatives
HK1160847A1 (en) Process for the preparation of piperazine derivatives
IL202995A (en) One pot method for n-demethylation of an n-methylated morphine alkaloid
ZA201100760B (en) Process for the preparation of benzoimidazol-2-yl pyrimidine derivatives
HK1201441A1 (en) Process for the preparation of substituted pyrimidine derivatives
AU2009254929A8 (en) An improved process for the preparation of amines
ZA201006884B (en) Process for the preparation of donepezil hydrochloride
IL205082A0 (en) Process for the preparation of tetranorlabdane derivatives
EP2276740B8 (en) Improved process for preparing quinoline-3-carboxamide derivatives
IL206571A0 (en) Process for the preparation of an enantiomeric triubstituted 3,4-dihydro-isoquinoline derivative
EP2481734A4 (en) Method for preparing halofuginone derivative
IL194389A0 (en) Process for preparing heterocyclic derivatives
PL2342206T3 (en) Processes for the hydrogenation of opiate alkaloid derivatives
EP2507212A4 (en) Process for preparing methyl phenidate hydrochloride

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880007353.7

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2008726581

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2009552750

Country of ref document: JP

Ref document number: 2008223328

Country of ref document: AU

Ref document number: 2680205

Country of ref document: CA

Ref document number: 579469

Country of ref document: NZ

Ref document number: 5214/CHENP/2009

Country of ref document: IN

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2008223328

Country of ref document: AU

Date of ref document: 20080306

Kind code of ref document: A

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08726581

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 12529723

Country of ref document: US